There is a very special brown mouse in a small plastic cage on the table in Fabio Rossi’s lab at the University of B.C. The mouse carries the mutation for muscular dystrophy and is being used for biomedical research into human neuromuscular diseases.

The research requires that venom from the deadly Australian tiger snake be injected into the mouse’s muscle tissue with a fine syringe for study into its regenerative response.

“It burns,” allows Rossi, a professor of medical genetics and director of UBC’s Biomedical Research Centre. “I’ve stuck myself a few times. I know what the animals feel. If these poisons reach your heart, you’re a dead man. But the amounts we inject would never reach the heart.”

On a five-step scale of pain and suffering, the procedure ranks second-highest, causing moderate to severe distress or discomfort.

“They’re not perfect. They’re not humans, of course. But they’re close enough that they are our best shot at finding places where we can intervene in human diseases to make it better.”

According to the Ottawa-based Canadian Council on Animal Care, member institutions used 4.3 million animals in research, teaching, and testing in Canada in 2016. That’s a 21-per-cent increased over the previous year, and a 50-per-cent increase over five years ago. Three types of animals — fish, mice and cattle — collectively accounted for 84 per cent of the total. Animals were researched in labs but also in the wild.

Council spokeswoman Sandra MacInnis said increases in funding can influence the creation and expansion of research programs and an increase in animal-based science. Other factors behind changes in animal use may include changes in funding priorities, regulatory changes, numbers and types of institutions certified by the council, development and implementation of new technologies, and changes in scientific interests.

Also behind the increase is a jump in the number of animals used in non-invasive studies, including feeding trials and animals used to train technicians, she added.

Even categories representing less than one per cent of the total involved a lot of animals. A total of 15,093 dogs — almost twice the number of cats — were used in research across Canada, along with 7,556 primates (mostly macaque monkeys) and 6,372 horses.

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Critics charge that Canada is lagging other countries in seeking alternatives to using animals in research, and suggest that universities, in particular, can be slow to change their ways.

“Animal research has been the foundation of biomedical research for the last 100 years,” says Charu Chandrasekera, executive-director of the Canadian Centre for Alternatives to Animal Methods and its subsidiary, the Canadian Centre for the Validation of Alternative Methods.

Charu Chandrasekera is executive-director of the newly opened Canadian Centre for Alternatives to Animal Methods at the University of Windsor.Frank Michael Photography /
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“It’s difficult to initiate culture change. It’s a paradigm shift that we need. We’re not ready to end animal testing tomorrow morning, but we certainly need to start moving in that direction.”

Chandrasekera’s centre is the first of its kind in Canada, opened four months ago at the University of Windsor, decades behind similar facilities in the U.S. and Europe. “Countries from Brazil to China have already established centres dedicated to the development … of alternatives to animals testing.”

She argues that an emphasis on animal research has actually set back advances in human health. “Overreliance on animal research has significantly hindered our understanding of human biology and disease, and made drug development and chemical safety testing a failure-prone endeavour.”

Change is rapidly underway in the U.S.

Francis Collins, director of the National Institutes of Health, told a congressional subcommittee that animal safety testing for environmental chemicals and drugs will largely be replaced by alternative research methods in a decade, citing results that are “more accurate, lower cost and higher throughput.”

And the U.D. Environmental Protection Agency has released a plan for moving away from vertebrate animals in the testing of chemical substances.

Elsewhere, the European Union has banned animal testing of cosmetics and has changed the legal status of animals from “things to sentient beings,” said environmental lawyer David Boyd, author of The Right of Nature and an associate professor at UBC.

New Zealand also bans experiments on great apes — gorillas, chimpanzees, orangutans and bonobos.

“We don’t have those laws in Canada yet, but it’s high time our legal system caught up with the science in terms of animal sentience and intelligence,” Boyd says.

In Canada in 2016, six gorillas were used for research that involved little or no discomfort or stress, according to the Canadian Council on Animal Care.

UBC says it conducted research causing minor stress or pain of short duration on macaque monkeys in 2016 related to Parkinson’s Disease and other neurodegenerative brain diseases.

According to Chandrasekera, too often research on animals does not translate to humans. Factors include differences in biological processes, disease mechanisms and drug responses.

“It’s been 100 years since (Dr. Alois) Alzheimer first described the disease. Despite extensive research at enormous expense, we still don’t understand the molecular basis of Alzheimer’s disease, much less a cure.” That’s despite the fact that Alzheimer’s has been cured hundreds of times in mice, she said.

She added that “95 per cent of drugs tested to be safe and effective in animals fail in human clinical trials” and in terms of toxicity testing for substances such as cosmetics, household cleaning products, pesticides, and industrial chemicals, rodents predict outcomes in humans at about 43-per-cent efficiency.

“You might as well flip a coin,” Chandrasekera said.

If a drug as commonly used today as Aspirin were to undergo modern-day drug testing, it “would never” be approved for humans since it causes birth defects in mice and other animals, she added.

Chandrasekeraan says researchers have a scientific and ethical mandate to replace, reduce and refine research involving animals — known as the Three Rs. “It’s just that the vast majority of time we don’t follow that. It’s just not on the priority list.”

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Alternatives to animal testing may include computer modelling and in vitro methods, those in a test tube or culture dish, that is outside a living organism, she said.

In the U.S., the Wyss Institute at Harvard University says that researchers have engineered microchips — called organ-on-chips — that mimic key functions of human organs, including the lung, intestine, kidney, skin, bone marrow and blood-brain barrier.

The Center for Alternatives to Animal Testing has been in business since 1981 at Johns Hopkins University in Baltimore. One of its latest developments involves the use of human stem cells to develop “mini-brains” that mimic the structure of the human brain — a form of organotypic cell culture that benefits people and animals.

Thomas Hartung is a researcher at the Center for Alternatives to Animal Testing, founded in 1981, at Baltimore’s Johns Hopkins University.JHU/CAAT /
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“We’re seeing a lot of progress in this field,” confirms Johns Hopkins researcher Thomas Hartung, noting that dozens of alternative research methods have been internationally accepted and validated.

While the European pharmaceutical industry’s share of animal use in research dropped to 19 per cent from 31 per cent from 2005 to 2011, he said, public pressure likely had little to do with it. “They simply see this is not the most-efficient strategy. This industry is forced to be efficient and uses any technology at hand.”

Ultimately, the differences between humans and animals are too great, he said, arguing that artificially introducing a disease is part of the problem. “We are not 70 kilogram rats.”

Still, Hartung does not discount the role that animals have played in research over the years.

“Animals have made our world a safer place. We have a lot of medicines developed with the help of animals. There is no doubt about it.” Drugs developed for animals will continue to be tested on animals, he said. And one cannot conduct behavioural studies in a test tube. But he predicted overall an increasing trend away from animal use.

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At his UBC lab, Rossi studies tissue regeneration and inflammatory cells in muscular dystrophy, multiple sclerosis and ALS, also known as Lou Gehrig’s Disease.

“How many different types of cells are involved and how do they communicate with each other?” he said. “If they don’t work together, it won’t end up well.”

Rossi also uses mice to study response to an induced heart attack. “We open the chest of the mouse, ligate (close off) a coronary artery — on a mouse that beats about 250 beats per minute, I can tell you that’s not an easy task — then close the mouse and follow it over time.”

Ian Welch, UBC’s director of veterinary services and research support, argues that the university has a rigorous process of screening research proposals involving animals.

Researchers do not like the idea of causing pain and stress to an animal, he said, and fully support finding alternatives. “It’s not an easy thing to do. It requires a lot of money and expertise.”

As for the transferability of animal research to humans, he said: “It is hit and miss, but think of any vaccine you’ve ever taken, any medical device you’ve ever received or been plugged in to that is monitoring your body — all of those things were tested in animals before you ever saw them.

“I’m of the opinion those are good things and critical to the health of our society.”

Welch argued that animal research numbers are driven by the quest to find answers to human diseases. Animals are needed for basic research — understanding the disease before moving to the next phase, applied research including for drug tests.

“It’s the testing in animals that leads a drug supplier to get permission to test it in humans, the clinical trials that determine whether it can be sold to the public.”

He argued that researchers at UBC are aggressively looking to the future and that agencies won’t fund research projects unless a good argument can be made for the use of animals. “If you live in the past, you’re done as an academic researcher.”

In Canada, 57 per cent of the 4.3 million animals were used in “studies of a fundamental nature/basic research,” which closely captures what universities do.

Another 14 per cent were used for the development of products or appliances for human or veterinary medicine; 13 per cent were for medical purposes, including veterinary medicine, related to human or animal diseases or disorders; 10 per cent for education and training in post-secondary institutions or facilities; and six per cent for regulatory testing of products for the protection of humans, animals, or the environment.

The Canadian Council on Animal Care, which had a budget of almost $2.7 million last year, includes several B.C. institutions — UBC, Douglas College, Bamfield Marine Sciences Centre, Thompson Rivers University, Trinity Western University, University of the Fraser Valley, University of Victoria, Vancouver Island University, and Simon Fraser University.

The council’s major national funders include the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council.

Sitting among the research scientists on the council’s board of directors is Shawn Eccles, senior manager of cruelty investigations for the B.C. SPCA.

He said he strongly believes in greater openness and accountability, urging all institutions to reveal the nature of their experiments. “It’s an area of concern for me,” he said.

Eccles is also troubled by the fact federally funded institutions are required to be members of the council, but some private facilities conduct research on animals without the same reporting requirements. The council does not track non-member research facilities, but suggests they might include smaller biotech firms conducting research and development as well as contract research organizations.

“It certainly is troubling. There’s a lot of research out there with no requirement to record their information, their studies, or the numbers of animals being used to the CCAC.”

UBC posts animal research statistics annually on its website.

In 2016, the institution used 167,019 animals, down 10 per cent from 2015 — and none were E-level experiments, the most invasive and painful category of research. “Trying to get an E protocol through our animal care committee would be a fool’s errand,” Rossi says.

Simon Fraser University said it used 26,869 animals in 2016, a drop of 6.5 per cent over 2015, and that numberincludes “field surveys, etc., in which literally thousands of animals are captured and released, as well as only observed in the wild.”

The University of Victoria’s use of animals jumped significantly, to 137,606 in 2016, from 23,447 in 2015, due largely to “large population studies of fish in coastal and international waters.”

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Among the reasons Rossi cites for using mice for his research: It is easy to modify their DNA; most antibodies and strains carrying specific mutations are mouse-specific at the moment; a quick regeneration cycle, which allows for fast breeding of mice carrying different mutations (natural or engineered); and relatively low costs to house compared with larger animals.

Even mice don’t come cheap. His mouse budget is $12,000 to $14,000 a month, reflecting the cost of bringing the mice up specially from the U.S. The lab has a staff of 12 to 18, depending on funding.

“My typical day is spent in front of a computer writing grant (requests) to pay for my mouse bill.” A special courier company is employed to ensure the mice arrive in good condition. He notes it’s important to avoid unnecessarily stressing an animal, since that can alter the results of an experiment.

For now, Rossi argues there is no other choice if the public wants scientists to find answers to complicated biological processes such as regeneration.

“You can do a lot with embryonic stem cells, in vitro these days and in the future those will become the models of choice. But it’s going to take a couple of decades before we get there.

“As researchers, we would not use animals if we didn’t have to, for budgetary reasons and it’s not something we enjoy doing, giving a disease to a little animal. We have to do it to get the answers to certain questions.”

The Canadian Council on Animal Care reports that 1.2 million animals, or 28 per cent of the total, were subjected to moderate to severe distress or discomfort in 2016.

And 97,455, or two per cent, experienced severe pain, E-level experiments. The categories of animals that suffered the greatest pain included Atlantic salmon, chickens, leopard frogs, striped bass, trout, and sticklebacks.

The council won’t reveal exactly what researchers did to those animals, saying that’s up to individual institutions to reveal. And they aren’t about to make it easy for the public to know.

Welch said anyone who wants to know more can do an internet search of researchers’ names and read their published studies — an onerous task, with the prospect of having to pay to read the full research papers. “It would involve you going to a computer and typing a person’s name in,” he said.

Rossi is a rare scientist prepared to speak publicly about his research with animals, and he favours greater openness despite concerns about being targeted by animal rights groups. UBC made it a condition of Postmedia News’ interview with Rossi that the exact location of his lab not be revealed.

“There has been a culture of secrecy in institutions for too many years,” Rossi says. “We’re quite proud of what we do. We’re not ashamed.”

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